Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6, (IL-6), interleukin-1 beta (IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas.
Ovarian carcinoma is often associated with overexpression of cytokines that may exert autocrine and paracrine growth effects, as well as genetic alterations in (proto)oncogenes and tumour suppressor genes, such as p53. The p53 protein is not only involved in the regulation of cell cycle and apoptosis, it is also involved in the in vitro regulation of IL-6 gene expression. In this study, 30 tumours of patients with a primary diagnosis of human ovarian carcinoma were characterised for p53 expression with immunohistochemistry and analysed for the expression of M-CSF, IL-6, IL-1 beta, IL-11 and TNF-alpha with Northern blotting. Nuclear and cytoplasmic p53 staining was observed in 27% (8/30), cytoplasmic staining in 30% (9/30), and no p53 staining in 43% (13/30) of the tumours. In 70% (21/30) of the tumours, M-CSF mRNA was expressed, in 40% (12/30) TNF-alpha, and in 30% (9/30) IL-6. None of the tumours expressed IL-1 beta or IL-11. The expression of TNF-alpha occurred more frequently in M-CSF positive tumours compared to M-CSF negative tumours (52% (11/21) versus 11% (1/9), P < 0.05). TNF-alpha expression was also associated with better responses to chemotherapy (P < 0.02). M-CSF expression was associated with nuclear p53 staining (P < 0.05). The p53 positive tumours more frequently expressed one or more cytokines (88%) compared with p53 negative tumours (54%, P < 0.05). This study suggests that mutations in the p53 gene might be associated with cytokine overexpression, especially M-CSF.
Asschert
J G
JG
Division of Medical Oncology, University Hospital Groningen, The Netherlands.
Vellenga
E
E
Hollema
H
H
van der Zee
A G
AG
de Vries
E G
EG
D000230:Adenocarcinoma / Q000378:metabolism*; D015152:Blotting, Northern; D016207:Cytokines / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016207:Cytokines; D007378:Interleukins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D016173:Macrophage Colony-Stimulating Factor